The principal objective of this research is to obtain quantitative data on dose-response relationships for the induction of mutation in an in vitro mammalian cell system. CHO and HeLa cells will be selected for their resistance to 8-azaguanine, a toxic analogue which selects for a mutation in the gene for hypoxanthineguanine phosphoriboxyl transferase; and to ouabain, which in its binding to ATPase is toxic to wild-type cells. Factors which influence the quantitative nature of the mutation system, such as drug concentration, cell density and expression time, will be carefully controlled to obtain accurate responses. The mutation induction by x-rays will be determined for different stages of the cell cycle, various dose-rates and fractionations. The possible influence of hyperthermia on mutation production will be investigated. Various agents and treatments will be used to measure the repair of the mutation lesions in comparison with that of the lethal lesion. An analysis of mutants selected under several conditions will be aimed at determining the nature of the mutation lesion.